Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory.

Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory.
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NR2A:NR2B 比率增加会压缩长期抑郁范围并限制长期记忆。

DOI:
10.1038/srep01036
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Tsien, Joe Z.
Tsien, Joe Z.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cui, Zhenzhong;Feng, Ruiben;Jacobs, Stephanie;Duan, Yanhong;Wang, Huimin;Cao, Xiaohua;Tsien, Joe Z.

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众所周知,NMDA受体的NR 2A:NR 2B亚基比例在出生后发育到性成熟和衰老的大脑中增加,但其对记忆功能的影响仍然是推测性的。我们已经产生了前脑特异性NR 2A过表达转基因小鼠,并表明这些小鼠具有正常的基本行为和短期记忆,但表现出广泛的长期记忆缺陷,如几种行为范式所揭示的。令人惊讶的是,增加NR 2A的表达并没有影响1赫兹诱导的长时程抑郁(LTD)或100赫兹诱导的长时程增强(LTP)在海马CA 1区,但选择性地取消LTD反应在3-5赫兹的频率范围。  我们的研究结果表明,增加NR 2A:NR 2B比例是限制成人大脑长期记忆的关键遗传因素。我们假设,LTD样过程的基础上学习后的信息塑造,一个新的和必要的巩固步骤,在新的信息转化为长期记忆。
The NR2A:NR2B subunit ratio of the NMDA receptors is widely known to increase in the brain from postnatal development to sexual maturity and to aging, yet its impact on memory function remains speculative. We have generated forebrain-specific NR2A overexpression transgenic mice and show that these mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms. Surprisingly, increased NR2A expression did not affect 1-Hz-induced long-term depression (LTD) or 100 Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3–5 Hz frequency range. Our results demonstrate that the increased NR2A:NR2B ratio is a critical genetic factor in constraining long-term memory in the adult brain. We postulate that LTD-like process underlies post-learning information sculpting, a novel and essential consolidation step in transforming new information into long-term memory.
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